Multifunctional nanosystems for precision diagnosis and detoxification in cardiovascular diseases: From multimodal imaging of myocarditis to cardioprotective chemotherapy

Background and Objective: Early diagnosis and cardioprotection remain key challenges in the management of inflammatory and chemotherapy-induced cardiac injuries. To address these, our research team has developed macrophage membrane-modified nanoparticles (MM/NPs) to guide early non-invasive diagnosis of myocarditis from a multimodal imaging perspective. Additionally, we engineered a dual-functional synergistic nanoplatform (PGPP/NPs) with both cardioprotective and antitumor capabilities to tackle doxorubicin-induced cardiotoxicity (DIC).

Methods: (1) Diagnostic Nanoprobe (MM/NPs): Fabricated macrophage membrane (MM)-camouflaged phase-change nanoparticles via double emulsion and liposome extrusion, loaded with SPIO (T?-MRI) and PFH (PA/US contrast agents).Validated targeting specificity in experimental autoimmune myocarditis (EAM) mice using confocal imaging, flow cytometry, and multimodal imaging. (2)?Therapeutic Nanocomplex (PGPP/NPs): Engineered carrier-free self-assembled nanoparticles co-loaded with ginsenoside Rb1 (antioxidant), probucol (anti-inflammatory), and PI3Kγ inhibitor (autophagy enhancer), surface-functionalized with cardiomyocyte-targeting peptide (PCM). Evaluated cardioprotection in a 4T1 breast cancer model undergoing DOX chemotherapy, assessing cardiac function, serum biomarkers, and autophagic flux.

Results: (1) Diagnostic Performance: MM/NPs achieved high targeting efficiency in EAM myocardium (p<0.05), enabling simultaneous US/PA/MRI imaging with superior contrast to non-targeted controls. Multimodal imaging revealed inflammatory foci and myocardial damage, correlating with histopathological findings. (2) Therapeutic Efficacy: PGPP/NPs selectively accumulated in cardiomyocytes, reducing DOX-induced oxidative stress (ROS↓), inflammation (TNF-α↓, IL-6↓), and apoptosis (caspase-3↓) while enhancing autophagy (LC3-II↑). Cardiac function (LV-EF/LV-FS) and serum biomarkers (cTnI, BNP) normalized in PGPP/NP-treated mice, with preserved DOX antitumor activity (p<0.05 vs. free DOX).

Conclusion: This integrated nanomedicine strategy bridges diagnostic imaging and therapeutic intervention. MM/NPs enable early, non-invasive detection of myocardial inflammation through multimodal imaging. PGPP/NPs reconcile cardioprotection with chemotherapeutic efficacy via antioxidant, anti-inflammatory, and autophagy-modulating mechanisms. This dual-platform approach holds transformative potential for precision cardio-oncology and inflammatory heart disease management.

To be updated shortly..